We have recently uncovered a new, epidemic disease, Lyme disease, probably caused by an infectious agent transmitted by Ixodes dammini ticks. In Lyme disease, immune complex formation is associated with lesions in the skin, joints, heart, or nervous system. We plan to define the natural history of this illness, its course and prognosis, etiology, vector, and pathogenesis. To accomplish these objectives, a surveillance network of primary physicians has been established to refer patients with Lyme disease; the natural history of the illness will be described from the serial examination of these patients. All patients will be contacted at least yearly to gain information about recurrent symptoms. All cases reported to use from physicians outside Connecticut will be computed to determine the geographic distribution of the disease in the United States. Immune complexes and cryoprecipitates will be sought for in the sera of each patient at each visit, and characterized. In collaboration with Dr. Robert Winchester at Rockefeller University, complete immunogenetic profiles will be done on selected patients and their families. The natural cycle and preferred hosts of Ixodes dammini will be studied in the field. Ixodes dammini collected in the field will be pooled and extracts inoculated into tissue cultures, mice, and monkeys. Tissue culture cells and skin biopsy specimens will be examined by indirect immunofluorescence. Immune complexes will be fractionated and an attempt made to identify putative antigens. If a serologic test can be developed for Lyme disease, positive diagnosis will be possible in all affected patients, and studies will be conducted to determine attack rates within sample human and animal populations. The results would provide the basis for decisions about control measures.